Tuberc Respir Dis.  2010 Feb;68(2):55-61. 10.4046/trd.2010.68.2.55.

Role of the PLA2-Activated Neutrophilic Oxidative Stress in Oleic Acid-Induced Acute Lung Injury

• Lee YM
• Kim BY
• Park YY

• KMID: 2050585
• DOI: http://doi.org/10.4046/trd.2010.68.2.55

Abstract

BACKGROUND
The underlying pathogenesis of fat embolism-induced acute lung injury (ALI) has not been elucidated. In the present study, the pathogenesis of fat embolism-induced ALI was probed in association with neutrophilic oxidative stress in oleic acid (OA)-induced ALI of S-D rats.
METHODS
OA was injected intravenously to provoke ALI in experimental rats. Five hours later, indices of ALI were measured to confirm the role of the neutrophilic respiratory burst. The effect of an inhibition of phospholipase A2 (PLA2) was also evaluated.
RESULTS
The accumulation of neutrophils in the lung due to OA caused increased neutrophilic oxidative stress in lung, which was ameliorated by mepacrine. What were the results from inhibition of PLA2.
CONCLUSION
Excess neutrophilic oxidative stress contributes to OA-induced ALI, which is lessened by the inhibition of PLA2.

Keyword

Acute Lung Injury; Embolism, Fat; Neutrophils; Phospholipase A2

MeSH Terms

Acute Lung Injury
Animals
Embolism, Fat
Lung
Neutrophils
Oleic Acid
Oxidative Stress
Phospholipases A2
Quinacrine
Rats
Respiratory Burst
Oleic Acid
Phospholipases A2
Quinacrine

Figure

• 

  Figure 1 Microscopic finding of OA-neutrophil aggregate after NBT reaction in vitro. Massive accumulation of formazan-positive neutrophils (asterisk) was noted at the vicinities of OA droplets (arrows). Original magnification ×100.

• 

  Figure 2 Morphological evidence of chemotactic activity of OA on neutrophils. Around OA droplets (asterisk), dense accumulation of formazan positive neutrophils was noted. Almost all the neutrophils were formazan positive. The accumulation of neutrophils at the vicinities of OA droplets was much more dense compared with that of the remote area from OA droplets (arrow head). Original magnification ×40.

Reference

1. Ware LB, Matthay MA. The acute respiratory distress syndrome. N Engl J Med. 2000. 342:1334–1349.

2. Bernard GR. Acute respiratory syndrome: a historical perspective. Am J Respir Crit Care Med. 2005. 172:798–806.

3. Zhou Z, Kozlowski J, Schuster DP. Physiologic, biochemical, and imaging characterization of acute lung injury in mice. Am J Respir Crit Care Med. 2005. 172:344–351.

4. Liu H, Zhang D, Zhao B, Zhao J. Superoxide anion, the main species of ROS in the development of ARDS induced by oleic acid. Free Radical Res. 2004. 38:1281–1287.

5. Hill LL, Chen DL, Kozlowski J, Schuster DP. Neutrophils and neutrophil products do not mediate pulmonary hemodynamic effects of endotoxin on oleic acid-induced lung injury. Aneth Analg. 2004. 98:452–457.

6. Tighe D, Moss R, Boghossian S, Heath MF, Chessum B, Bennett ED. Multi-organ damage resulting from experimental faecal peritonitis. Clin Sci (Lond). 1989. 76:269–276.

7. Dana R, Malech HL, Levy R. The requirement for phospholipase A2 for activation of the assembled NADPH oxidase in human neutrophils. Biochem J. 1994. 297:217–223.

8. Jaeschke H, Smith CW. Mechanisms of neutrophil-induced parenchymal cell injury. J Leukoc Biol. 1997. 61:647–653.

9. Bulger EM, Maier RV. Lipid mediators in the pathophysiology of critical illness. Crit Care Med. 2000. 28:N27–N36.

10. Babior BM. Phagocytes and oxidative stress. Am J Med. 2000. 109:33–44.

11. Haslett C, Guthrie LA, Kopaniak MM, Johnston RB Jr, Henson PM. Modulation of multiple neutrophil functions by preparative methods or trace concentrations of bacterial lipopolysaccharide. Am J Pathol. 1985. 119:101–110.

12. Botha AJ, Moore FA, Moore EE, Fontes B, Banerjee A, Peterson VM. Postinjury neutrophil priming and activation states: therapeutic challenges. Shock. 1995. 3:157–166.

13. Shiue S, Thrall RS. Effect of corticosteroid therapy on the acute lung injury and recovery stage of oleic acid induced lung injury in the rat. Exp Lung Res. 1991. 17:629–638.

14. Goldblum SE, Wu KM, Jay M. Lung myeloperoxidase as a measure of pulmonary leukostasis in rabbits. J Appl Physiol. 1985. 59:1978–1985.

15. Brown RE, Jarvis KL, Hyland KJ. Protein measurement using bicinchoninic acid: elimination of interfering substances. Anal Biochem. 1989. 180:136–139.

16. McGuigan RM, Mullenix P, Norlund LL, Ward D, Walts M, Azarow K. Acute lung injury using oleic acid in the laboratory rat: establishment of a working model and evidence against free radicals in the acute phase. Curr Surg. 2003. 60:412–417.

17. Dana R, Leto TL, Malech HL, Levy R. Essential requirement of cytosolic phospholipase A2 for activation of the phagocyte NADPH oxidase. J Biol Chem. 1998. 273:441–445.

18. Repine JE. Scientific perspectives on acute respiratory distress syndrome. Lancet. 1992. 339:466–469.

19. Lee YM, Hybertson BM, Terada LS, Repine AJ, Cho HG, Repine JE. Mepacrine decreases lung leak in rats given interleukin-1 intratracheally. Am J Respir Crit Care Med. 1997. 155:1624–1628.

20. Furue S, Kuwabara K, Mikawa K, Nishina K, Shiga M, Maekawa N, et al. Crucial role of group IIA phospholipase A2 in oleic acidinduced acute lung injury in rabbits. Am J Respir Crit Care Med. 1999. 160:1292–1302.

21. Young JS, Rayhrer CS, Edmisten TD, Cephas GA, Tribble CG, Kron IL. Sodium nitroprusside mitigates oleic acid-induced acute lung injury. Ann Thorac Surg. 2000. 69:224–227.

22. Vadász I, Morty RE, Kohstall MG, Olschewski A, Grimminger F, Seeger W, et al. Oleic acid inhibits alveolar fluid reabsorption: a role in acute respiratory distress syndrome? Am J Respir Crit Care Med. 2005. 171:469–479.